The Pittsburgh Cancer Institute proposes to organize a SPORE for gastrointestinal cancer (PCI-GIS) with the overall objective of devising effective strategies for treating both limited ("early") and advanced disease. The primary focus of these projects will be colorectal and pancreatic cancers, the most common of gastrointestinal malignancies.The proposed research projects are closely interconnected and involve a wide array of basic and clinical expertise, that is being focused on gastrointestinal cancer. All four projects are directed towards the development and understanding of new therapeutic strategies for these tumors. Project 1 will examine the potential for active immunization against colorectal and pancreatic cancer associated mucins. Project 2 will examine the factors which influence the accumulation of cytotoxic effector cells within hepatic metastases and approaches to enhancing the therapeutic effects of these cells when used as regional therapy. Project 3 will evaluate the efficacy of a new class of therapeutic agents - monoclonal antibody directed against cell surface antigens linked to the potent cytotoxic compounds, enedyienes. Project 4 will investigate the role of gastrin as a modulator of cell growth and proliferation in normal and neoplastic colonic epithelial cells. Each of these projects is closely linked or in fact dependent on clinical trials being conducted in parallel to the laboratory-based investigations; the findings in these projects offer the prospect for translation to new clinical initiatives in colorectal and pancreatic cancer. In addition to the research studies proposed, the PCI-GIS will establish a series of key resources to support research on gastrointestinal cancer, including a Tissue/Serum Bank and a Biostatistics Unit. The initiation of promising research pilot projects will also be encouraged and facilitated. Overall, the proposed PCI-GIS will lead to the development of new approaches to the treatment of colorectal and pancreatic cancers -approaches which may have applications not only in the therapy of established metastatic or regionally confined disease, but offer the prospect for defining approaches to the prevention of invasive or metastatic colorectal and pancreatic cancers.